Background and Research Goals. This study aims to see the association between worldviews and HPV vaccine risk perceptions in a sample of Canadian undergraduate students enrolled in Health Sciences and Business programs at the University of Ottawa. It is a follow-up to the Kahan et al. (2010) research in the U.S. that showed the association to be present in a nationally representative U.S. sample. In addition to searching for this association in the Canadian context, this study examines whether worldviews differ between (a) men and women; and (b) students with health sciences and with business degrees. Furthermore, this study tests a set of candidate questions for supplementing the worldview questionnaire of Kahan et al. (2010). Design and Analysis. The data for the study was collected using an Internet-based questionnaire and the study was conducted in two phases. During the first phase, a customized worldview questionnaire was administered. During the second phase, questions related to HPV and Canadian healthcare system were presented. In order to analyze the data, regression models, correlation matrices, and MANOVAs were employed. Results. The findings of this study are that worldviews are related to HPV vaccine risk perceptions. However, though hierarchism was a better predictor then individualism in the Kahan et al. (2010) study, our present research indicates that individualism is a better predictor. Also, our findings, contrary to those of Kahan et al. (2010), suggest that the more individualistic a person is, the more likely he or she is to perceive the vaccine as being safe. With respect to gender, men were more hierarchical. Also, when females in health sciences were compared to women in business, the latter were also more hierarchical. Finally, three healthcare items were identified as possibly benefiting from refinement and inclusion in a worldview instrument more suited for the Canadian context.

The incidence of human papillomavirus (HPV) -associated oropharyngeal tumors is steadily increasing therefore, information about the prevalence of oral HPV and its risk factors is very important for future screening and early diagnosis of the disease. This thesis addresses three topics. The first topic is to evaluate the prevalence of oral HPV in a healthy population and to investigate risk factors for oral HPV infection, given that these data are almost completely absent in Central Europe. A statistically significantly higher rate of positivity (8.8%) of oral HPV infection was found in the group of older unvaccinated probands than in younger partially vaccinated volunteers (2.0%). The seropositivity rate of anamnestic HPV antibodies was comparable in both groups. None of the analyzed risk factors were significantly associated with oral HPV positivity. The second topic of the thesis is the dynamics of HPV specific antibodies in patients with head and neck cancer and their prognostic significance. In patients with cervical cancer, a decrease in HPV E6 / E7-specific antibodies is associated with a better prognosis. Another goal of the dissertation was to assess the importance of anamnestic antibodies and antibodies against oncoproteins E6 and E7 in long-term follow-up 2-14 years after the end of...

Indiana University-Purdue University Indianapolis (IUPUI) / Human papillomaviruses (HPVs) are non-enveloped, circular double-stranded DNA viruses that infect basal keratinocytes of stratified squamous epithelia. High-risk HPV (HR-HPV) infection causes nearly all cervical cancers and an increasing number of head and neck cancers. While prophylactic vaccinations have reduced the incidence of HPV infection and attributable cancers, currently there is no cure for pre-existing HPV infection. As such, HPV remains a global health threat and a better understanding of HPV biology remains of significant medical importance for identification of novel therapeutic targets. The multi-subunit structural maintenance of chromosomes 5/6 complex (SMC5/6) is comprised of SMC5, SMC6 and NSE1-4. SMC5/6 is essential for homologous recombination DNA repair and reportedly functions as an antiviral factor during hepatitis B and herpes simplex-1 viral infections. Intriguingly, SMC5/6 has been found to associate with HR-HPV E2 proteins, which are multifunctional transcription factors essential to regulation of viral replication and transcription. The function of SMC5/6 associations with E2, as well as its role during HR-HPV infection remain unclear and we explored this question in the context of HR-HPV- 31. SMC6 interacted with HPV-31 E2 and co-immunoprecipitation of SMC6/E2 complexes required the E2 transactivation domain, inferring SMC6 association is limited to the full-length E2 isoform. Depletion of SMC6 and NSE3 increased HPV replication and transcription in keratinocytes stably maintaining episomal HPV-31, suggesting that the SMC5/6 complex represses these processes. Neither SMC6 nor NSE3 co-IP the viral E1 DNA helicase alone or E1/E2 complexes but the association of SMC6 with E2 was reduced in the presence of E1, indicating that SMC6 competes with E1 for E2 binding. This infers that SMC6 repression of the viral replicative program may involve inhibiting initiation of viral replication by disrupting E2 interactions with E1. Chromatin immunoprecipitation determined that SMC6 is present on episomal HPV-31 genomes, alluding to a possible role for SMC5/6 in modifying the chromatin state of viral DNA. Taken together, these findings describe a novel function for SMC5/6 as a repressor of the HPV-31 replicative program.

SUMMARYHuman papillomaviruses (HPV) are small, non-enveloped viruses with a dsDNA genome. About 40 HPV types infect the mucosa and skin of the anogenital tract, and they are further subdivided into low-risk HPV (LR-HPV) and high-risk HPV (HR-HPV). Long-term, persistent infections with the latter type could result in the development of cervical cancer. Cervical cancer is the second most prevalent cancer worldwide, and the third leading cause of cancer-related deaths in women. HR-HPV DNA is frequently found integrated in cervical carcinoma tissue. Thus, HR-HPV integration is considered to be mechanistically linked to virus-promoted malignancy. Several complex and sometimes inter-linked signal transduction pathways, collectively termed as the DNA Damage Response (DDR), act to sense damage incurred to DNA and ultimately promote its repair. The central players of the DDR are three proteins of the phosphatidylinositol 3-kinase-like protein kinase (PIKK) family, ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3-related (ATR) and DNA protein kinase catalytic subunit (DNA-PKcs). Also crucial to the DDR are members of the poly(ADP)ribose polymerase family (PARP). Interactions between histones modified by PARP enzymes, the PARP enzymes themselves and the X-ray repair cross-complementing protein (XRCC-1), are important for efficient DNA repair. Reversible acetylation of histones plays a key role in the regulation of gene expression and in the DDR. The acetylation of histones, as well as that of numerous other cellular proteins, is carried out by histone acetyl transferases (HAT). This enzymatic process exists in a tightly-regulated equilibrium with lysine deacetylation, which is catalyzed by histone deacetylases (HDAC). HDAC modulate the expression and/or function of key proteins implicated in cancer. In addition, many HDAC are overexpressed in most cancers. Various small-molecule inhibitors of HDAC have been developed. HDAC inhibitors (HDACi) have been shown to promote cancer cell cycle arrest, differentiation and apoptosis. In addition, HDACi are well-documented for their synergistic or additive effects on DNA-damaging agents used in cancer therapy. In spite of a growing body of research however, the cellular and molecular mechanisms behind this phenomenon have not yet been fully uncovered. We evaluated the impact of several pan-HDACi and HDACi analogues on the extrachromosomal and genomically-integrated HPV-16 LCR-driven transcription in various cell lines. Using a classical reporter construct strategy, we report that the pan-HDACi Trichostatin A (TSA), valproate (VPA) and sodium butyrate (NaB) are potent inducers of transcription from the HPV-16 long control region (LCR) in its extrachromosomal form. This effect of HDACi was at least in part mediated by three binding sites of members of the AP-1 family of transcription factors within the viral LCR. HDACi analogues 1 through 6 did not modulate extrachromosomal HPV-16 LCR transcription in a statistically-significant way. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

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Immunization is the most successful method in preventing and controlling infectious diseases, which has helped saving millions of lives worldwide. The discovery of the human papillomavirus (HPV) infection being associated with a variety of benign conditions and cancers has driven the development of prophylactic HPV vaccines. Currently, four HPV vaccines are available on the pharmaceutical market: Cervarix, Gardasil, Gardasil-9, and the recently developed Cecolin. Multiple studies have proven the HPV vaccines’ safety and efficacy in preventing HPV-related diseases. Since 2006, when the first HPV vaccine was approved, more than 100 World Health Organization member countries reported the implementation of HPV immunization. However, HPV vaccination dread, concerns about its safety, and associated adverse outcomes have a significant impact on the HPV vaccine implementation campaigns all over the world. Many developed countries have successfully implemented HPV immunization and achieved tremendous progress in preventing HPV-related conditions. However, there are still many countries worldwide which have not created, or have not yet implemented, HPV vaccination campaigns, or have failed due to deficient realization plans associated with establishing successful HPV vaccination programs. Lack of proper HPV information campaigns, negative media reflection, and numerous myths and fake information have led to HPV vaccine rejection in many states. Thus, context-specific health educational interventions on HPV vaccination safety, effectiveness, and benefits are important to increase the vaccines’ acceptance for efficacious prevention of HPV-associated conditions.

Forskning om stickrädda barn i elevhälsovården bedöms som otillräcklig, men betydelsefull då många vaccinationer sker i skolan. Syftet var att undersöka flickors upplevelser kring HPV- vaccination i elevhälsovården. Uppsatsstudien hade en mixad metod design och studien var baserad på enkätsvar från 14 flickor i årskurs fem och sex. Det kvantitativa resultatet visade att hälften av flickorna skattade sig som rädda i samband med HPV-vaccination och av dem skattade sig 42 % som livrädda. Upplevd smärta och rädslan för eventuell smärta var de faktorer flickorna uppgav skapade rädsla. Att ha en förälder och/eller en kompis med sig vid vaccinationen var enligt flickorna de viktigaste strategierna för att kunna minska deras rädsla. Det fanns en positiv korrelation mellan flickornas skattade rädsla och hur de upplevde att de inte kunde koncentrera sig på skolarbetet under hela veckan innan vaccination (r2=0,761; p=0,002). Det kvalitativa resultatet visade att flickorna upplevde starka fysiska och psykiska reaktioner såsom gråt, illamående, panik och stress, orsakade av rädsla inför, under och efter vaccinationen. Då elevhälsvårdens övergripande mål handlar om att förebygga både fysisk och psykisk ohälsa för barn och ungdomar är det viktigt att belysa problematiken med stickrädsla. Sammanfattningsvis behövs vidare forskning genomföras. Detta för att bättre kunna förstå hur omfattande stickrädsla är bland skolelever och för att sätta elevernas perspektiv i fokus. / Research on children with fear of needles in the student health service is estimated as inadequate but important because many vaccinations take place at school. The aim was to examine girls’ experiences of HPV-vaccination in student health services. The study had mixed method design and the study was based on survey responses from 14 girls in the fifth and sixth grade. The quantitative results showed that half of the girls estimated themselves as frightened during HPV-vaccination, and 42 % rated themselves as terrified. The percieved pain and fear of eventuall pain were the factors in the girls' experiences of HPV- vaccination that caused fear. Having a parent and/or a friend present as support are the two most common strategies for reducing the fear during the HPV-vaccination, according to the girls. There was a positive correlation between the girls' estimated fear and their percieved ability to not be able to concentrate on schoolwork during the week prior to vaccination (r2= 0.761; p = 0.002). The qualitative results showed that before, during and after vaccination, strong physical and psychological reactions such as crying, nausea, panic and stress were caused by fear. The student health services overall goal is about preventing both physical and mental health of children and adolescents and therefor it is important to highlight the problem of fear of needles. Further research is therefor needed to better understand the extent of fear of needles among schoolchildren and focus on their perspective.

Background: Human Papilloma Virus (HPV) is the recognized main reason for developing cervical cancer. HPV vaccine given to females is the most effective prevention. Purpose: To investigate knowledge and beliefs about HPV, cervical cancer and HPV vaccine among young Thai females in north-eastern part of Thailand. Further, to discover potential differences between those stating having knowledge about HPV and cervical cancer (group SHK), and those stating not having knowledge about HPV and cervical cancer (group SNHK). Method: A cross-sectional survey using a questionnaire about knowledge and beliefs of HPV where 221 young Thai females, aged 18-21, participated. Orem’s self-care theory was used as theoretical framework. Result: Less than 50 % of the participants knew about visible signs and symptoms of HPV infection. However, over 70 % had knowledge regarding HPV´s relation to sexual activity. Internet was the greatest source of information about HPV. Participants had positive belief towards the vaccine and more than 95% wished to get vaccinated. Group SHK had more knowledge then group SNHK with significant difference in seven out of fourteen knowledge items, and showed more positive beliefs with significant difference in six out of sixteen belief statements. Conclusion: The overall level of knowledge about HPV and cervical cancer was insufficient. However, this did not affect the participant’s beliefs in the subject negatively. Health care should provide viable internet sites with information about HPV to ensure that young Thai females get requisites, enabling self-care on preventing HPV infections by vaccination. / Bakgrund: Humant Papillom Virus (HPV) är den erkänt främsta orsaken till livmoderhalscancer. Vaccinering av unga kvinnor är den erkänt mest effektiva preventionen. Syfte: Att undersöka kunskap och åsikter om HPV, livmoderhalscancer och HPV vaccin bland unga thailändska kvinnor i nordöstra Thailand. Vidare, att undersöka om det fanns några skillnader mellan dem som säger sig ha kunskap om HPV och livmoderhalscancer (grupp SHK) och de som säger sig inte ha någon kunskap om HPV och livmoderhalscancer (grupp SNHK). Metod: En tvärsnittsstudie med ett frågeformulär om kunskap och åsikter om HPV som 221 unga thailändska kvinnor, i åldern 18-21, besvarade. Dorotea Orems omvårdnadsteori användes som teoretisk ram. Resultat: Mindre än 50 % av deltagarna hade kunskap om symtom av en HPV infektion. Över 70 % hade kunskap om HPV och dess relation till sexuell aktivitet. Största källan för information om HPV var internet. Deltagarna hade positiva åsikter inför vaccinet, mer än 95 % skulle vilja vaccinera sig. Grupp SHK hade mer kunskap än grupp SNHK med signifikant skillnad i sju av fjorton kunskapsämnen, och visade mer positiva åsikter med signifikant skillnad i sex av sexton påståenden rörande åsikter. Slutsats: Nivån av kunskap rörande HPV och livmoderhalscancer är otillräcklig, men det påverkar inte unga thailändska kvinnors åsikter om HPV vaccin i negativ riktning. Hälso- och sjukvården bör erbjuda korrekta och trovärdiga websidor med information om HPV för att ge unga thailändska kvinnor de förutsättningar som krävs för egenvård i prevention av HPV infektion genom vaccinering.

Ο καρκίνος του τραχήλου της μήτρας (ΚΤΜ), αποτελεί παγκοσμίως έναν από τους συχνότερα εμφανιζόμενους καρκίνους στο γυναικείο πληθυσμό. Ο ΚΤΜ επιφέρει σημαντική ψυχολογική, κοινωνική και οικονομική επιβάρυνση στους ασθενείς και στα συστήματα υγείας. Η κυριότερη αιτία εμφάνισης της νόσου συσχετίζεται με τη μόλυνση από τον ιό των ανθρώπινων θηλωμάτων – HPV (Human papilloma virus). O HPV συγκαταλέγεται στους πιο συχνά σεξουαλικ ώςμεταδιδόμενους ιούς. Ένα από τα μεγαλυτερα βήματα της δημόσιας υγείας για την προφύλαξη του πληθυσμού έναντι του HPV και κατ’ επέκταση του καρκίνου του τραχήλου της μήτρας, είναι η εισαγωγή του εμβολίου στο Εθνικό Πρόγραμμα Εμβολιασμού. Στα παρακάτω κεφάλαια (θεωρητικό μέρος) γίνεται εκτενής περιγραφή της ιστοπαθολογίας του ΚΤΜ και της βασικής βιολογίας του HPV, καθώς επίσης και του μηχανισμού δράσης του εμβολίου έναντι του ιού. Εν συνεχεία, στο ειδικό μέρος της παρούσας διπλωματικής εργασίας παρατίθενται στοιχεία που αφορούν την ευαισθητοποίηση και την αποδοσχή του πληθυσμού για τον προληπτικό εμβολιασμό έναντι του ιού HPV. / -